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Type I Alexander disease (AxD) presents with paroxysmal neurodegeneration, refractory epilepsy, and encephalopathy in the first years of life and is associated with a poor prognosis. Although there is no treatment, mild symptomatic improvement has been reported in one case of adult Alexander treated with ceftriaxone, given its interaction with the mutant glial fibrillary acid protein (GFAP) responsible for the disease's pathogenesis. We describe a patient presenting with irritability starting at 2 months of age, initially attributed to gastroesophageal reflux. A ventriculoperitoneal shunt was placed at 3 months of age due to hydrocephalus secondary to aqueduct stenosis detected through an MRI scan, but the irritability persisted. At 5 months, a new brain MRI was performed due to irritability worsening, onset of abnormal ocular movements and seizures. In addition genetic testing was performed. AxD was diagnosed due to the mutation c.716G>A (p.Arg239His) in GFAP. Since irritability had worsened and had not responded to levomepromazine, treatment with amoxicillin (80 mg/kg/day) was attempted to modulate glutamate levels. The patient showed a striking improvement of irritability in 48 h that persisted over the next months. The patient had frequent daily seizures which did not respond to valproate, clonazepam, or phenobarbital. Perampanel, a postsynaptic AMPA receptor antagonist, was added to phenobarbital and he was seizure free for more than 3 months. Drugs modulating glutamate levels in the central nervous system, including β‐lactam antibiotics and perampanel, may have an important role in the symptomatic treatment of AxD and other neurodegenerative diseases where glutamatergic excitotoxicity is a pathogenic determinant. Plain Language Summary: Alexander disease is a rare and serious condition that affects the brain, often leading to neurodegeneration (brain damage), seizures, and other problems in early childhood. The disease is caused by a mutation in a gene called GFAP. There is no cure, and current treatments mainly focus on relieving symptoms. This article discusses the case of a baby who showed signs of irritability and seizures from a young age. The baby was diagnosed with Alexander disease after brain scans and genetic testing. Despite treatment with various drugs, the baby continued to experience seizures and irritability. The doctors decided to try amoxicillin, a common antibiotic, because of its potential to help control the disease by affecting a brain chemical called glutamate. Surprisingly, the baby's irritability improved within 2 days of starting amoxicillin, and the improvement lasted for several months. However, the seizures persisted until another medication, perampanel, was added. This combination controlled the baby's seizures for over 3 months. Unfortunately, the baby passed away at 13 months due to complications from the disease. However, doctors believe that drugs like amoxicillin and perampanel could be promising treatments for managing symptoms of Alexander disease and other similar brain conditions in the future, especially where excess glutamate plays a role in the damage. This case suggests that these treatments may help control irritability and seizures, offering hope for better management of this challenging disease. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the effectiveness and tolerability of brivaracetam (BRV) monotherapy in a large series of patients with epilepsy. Method: This was a multicenter, retrospective, observational, non‐interventional study in 24 hospitals across Spain. Patients aged ≥18 years who started on BRV monotherapy, either as first‐line or following conversion, at least 1 year before database closure were included. Patients were evaluated at baseline and at 3, 6 and 12 months after initiation of BRV monotherapy, in accordance with usual clinical practice at these centers. Data were collected retrospectively from patients' individual charts by participating physicians. The primary effectiveness and safety endpoints were the percentage of seizure‐free patients 1 year after initiation of BRV monotherapy and the proportion of patients reporting adverse events (AEs) over the complete follow‐up period. Retention rates and subpopulation analysis (levetiracetam switchers, elderly and different etiologies) were also investigated. Results: A total of 276 patients were included (48 with BRV as first‐line monotherapy and 228 who converted to BRV monotherapy). The overall retention rate in monotherapy at 12 months was 89.9% (87.5% for first‐line monotherapy group; 90.4% for conversion‐to‐monotherapy group). Seizure‐freedom rates at 12 months were 77.8% (75% for first‐line monotherapy group; 78.4% for conversion‐to‐monotherapy group). AEs occurred in 39.5% of patients at 12 months (35.4% for first‐line monotherapy group; 40.4% for conversion‐to‐monotherapy group). Most AEs were mild‐to‐moderate. The most frequent AEs were irritability (12.3%) and dizziness (10.1%). The most frequent AEs leading to BRV withdrawal were dizziness (1.8%) and memory problems (1.4%). Similar outcomes in terms of effectiveness and tolerability of BRV monotherapy were observed in patients switching from levetiracetam, those with different epilepsy etiologies, and elderly patients. Significance: BRV was effective and well tolerated both as first‐line monotherapy and following conversion to monotherapy in a real‐world setting of patients with epilepsy. Plain Language Summary: The goal of the medical treatment of epilepsy is to ensure best possible patient quality of life, by maximizing seizure control and minimizing medication toxicity. Brivaracetam (BRV) is a new‐generation epilepsy treatment that is well tolerated by patients. In our study, monotherapy with BRV reduced seizures in patients who had not received other treatments and in patients who switched from a previous treatment to BRV monotherapy. BRV was well tolerated and also effective in sensitive patients (i.e., the elderly and those who had epilepsy caused by a brain tumor or a brain injury). [ABSTRACT FROM AUTHOR]

Background: Neurological complications (NCs) are of major concern following hematological stem cell transplantation (HSCT), most of which present with seizures. Procedures: We performed a retrospective study (2002–2018) of patients undergoing HSCT in order to analyze the incidence and aetiologies related to seizures. Results: Of 155 children undergoing HSCT, 27 (17.4%) developed seizures at some point in 2 years of follow‐up. The most frequent etiologies were central nervous system (CNS) infection (n = 10), drug toxicity (n = 8), and vascular disease (n = 5). A statistically significant association was found between seizure and the HSCT type (lower risk for a related identical donor, p =.010), prophylactic or therapeutic mycophenolate use (p =.043 and.046, respectively), steroid use (p =.023), selective CD45RA+ depletion (p =.002), pre‐engraftment syndrome (p =.007), and chronic graft‐versus‐host disease (GVHD) severity (p =.030). Seizures predicted evolution to life‐threatening complications and admission to intensive care (p <.001) and higher mortality (p =.023). A statistically significant association was also found between seizures and sequelae in survivors (p =.029). Children who developed seizures had a higher risk of CNS infection and vascular disease (odds ratio 37.25 [95% CI: 7.45–186.05] and 12.95 [95% CI 2.24–74.80], respectively). Conclusions: Neurological complications highly impact survival and outcomes and need to be addressed when facing an HSCT procedure. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the usefulness of ictal electroencephalography ( EEG)-combined functional magnetic resonance imaging ( MRI) ( EEG-f MRI) in localizing epileptogenic zone in refractory neocortical focal epilepsy. Methods From the EEG-f MRI database of our institution including 62 adult patients, 14 (age 18-46 years) experienced some ictal event during the test. Data were segmented into 10-s blocks, and the results were analyzed by contrasting each block to the contiguous 10-s block from the onset of seizure onward, in all cases. In seizures lasting >10 s (five cases), a supplementary analysis was performed, contrasting each block to a baseline condition, in the framework of the general linear model ( GLM) of analysis. Regions of activations were compared to results from the different techniques performed during presurgical evaluation, such as SISCOM, positron emission tomography ( PET), and invasive subdural EEG monitoring. Key Findings Regarding the structural MRI findings, nine cases presented some lesion, with blood oxygen level- dependent ( BOLD) signal activation placed in the same location in eight of them (89%). SISCOM studies were performed in 11 patients; 5 were concordant with the increase in BOLD signal in a sublobar level, whereas in 3 cases the concordance was in a lobar level. Eleven patients underwent PET studies, being also concordant in a sublobar level in four of them and in a lobar level in four additional cases. Finally, invasive EEG evaluation was performed in three patients and all of them had the seizure-onset zone in the initial area of BOLD activation. Significance This study adds relevant information to support the integration of EEG-f MRI in the multidisciplinary presurgical workup in patients with refractory epilepsy. [ABSTRACT FROM AUTHOR]

Creatine transporter deficiency (CRTR-D) is a rare X-linked inherited disease belonging to the group of cerebral creatine deficiency disorders. Major clinical features include developmental delay and epilepsy. To date, fewer than 200 individuals with CRTR-D have been reported. As a result, there is little evidence for effective treatment. Available therapies are creatine precursors, with a mild effect on disease progression. Concerning epilepsy, standard management is recommended and no specific anti-seizure medication (ASM) has been shown to be effective in refractory cases. We report the case of a 28-year-old male patient with CRTR-D and childhood-onset refractory epilepsy. He had an average of 10-20 focal motor seizures with impaired consciousness per month. He had tried several ASMs without significant improvement. Treatment with cannabidiol (CBD) and clobazam (CLB) in combination was added. The patient became seizure-free from the first week, and up to 1 year of follow-up. Behavioral improvement was also noted by his caregivers. No adverse effects were reported. Very few cases of CRTR-D with refractory epilepsy have been reported. This calls for more extensive research and suggests a possible role for CBD in cerebral creatine metabolism and transport and valuable option for future studies. PLAIN LANGUAGE SUMMARY: Creatine transporter deficiency (CRTR-D) is a rare genetic disorder causing mental, behavioral, and movement problems. More than half of patients also have seizures, but because there are fewer than 200 known cases, it is difficult to know the best treatment options. We present a 28-year-old man with CRTR-D who had severe developmental delays and frequent seizures since childhood, despite trying many medications. After starting cannabidiol and clobazam, he has been seizure-free for a year. Sharing this success might help other people with CRTR-D benefit from similar treatments., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Introduction: The widespread application of magnetic resonance imaging (MRI) has brought with it an increase in the detection of alterations in the white matter of the central nervous system. AIM. To investigate the evolution of patients with no previous neurological symptoms, but in whom MRI findings are highly suggestive of multiple sclerosis (MS)., Patients and Methods: We conducted a descriptive study of 11 patients with MRI findings suggesting MS. A longitudinal follow-up was used to determine the radiological progression and conversion into an isolated neurological syndrome and clinically defined MS., Results: Eleven patients (seven females and four males) were identified, with a mean age of 36 years (range: 28-48 years), who had been submitted to an MRI scan due to headache (n = 2), radiculalgia (n = 3), traumatic brain injury (n = 1), syncope (n = 1), peripheral nervous pathology (n = 1) and epileptic seizures (n = 1). The mean number of Barkhof-Tintore criteria in the initial MRI scan was three. The oligoclonal band study was positive in six cases and in nine patients visual evoked potentials were performed (three pathological). The mean follow-up time was 2.9 years (range: 2 months-11.9 years). The mean amount of time elapsed between the first and the second MRI scan was 2.03 years. A radiological progression was identified in seven cases (five of them with gadolinium uptake). Five patients became cases of isolated neurological syndrome, with a mean amount of time since the initial MRI scan of 4.13 years. Of these, three patients presented conversion into clinically defined MS, two into the relapsing-remitting form (after an average of 8.54 years since the initial MRI scan) and another into the primary progressive form., Conclusions: The identification of incidental lesions that are highly suggestive of MS could help to constitute a group of subjects with an increased risk of developing MS.